Unpacking the Multi-level Drivers of Cardiotoxicity Disparities in Breast Cancer Survivors

摘要 乳腺癌存活率的提高在一定程度上是由于治疗方法的改进。然而，这些 治疗并不是没有轻微的到危及生命的副作用。例如，蒽环类化疗药物(例如： 阿霉素)和人表皮生长因子受体-2(HER-2)靶向治疗已被证明 导致心脏毒性(CTX)，或对心脏造成损害。这种副作用是非常令人担忧的，因为幸存者 死于心脏病的可能性比任何其他诊断都高，在以下方面存在种族差异： 环磷酰胺和心脏相关死亡的风险。已被证明导致心脏毒性的因素包括黑色 种族和合并症的存在。而心血管疾病文献中包括了 其流行的心理社会和社会文化因素以及其表现形式和表现的种族差异 进展，这些因素在环磷酰胺的背景下没有被探索。此外，癌症护理提供因素，包括 CTX的维护值得关注，因为可能有机会解决护理方面的差距或差异 这可能会加剧CTX的差距。解决心理社会和社会文化因素可能会提供 旨在缓解CTX差异的干预目标。在社会生态模式的指导下，我将进行 回顾分析和历史-前瞻性队列研究，以确定与种族差距有关的因素 在CTX里。在K99指导阶段，我将提取接受治疗的乳腺癌幸存者的电子医院数据 使用蒽环类药物化疗或HER-2靶向治疗来阐明社会人口学、临床和 与CTX发病和种族差异有关的维持因素(目标1)。在《目标2》中，我将深入进行 对接受和不接受CTX治疗的黑人和白人幸存者(n=20)进行访谈，以了解心理社会和 可能有助于CTX的社会文化经历。在R00阶段(目标3)，我将使用这些信息 从深度访谈中了解到的信息，将分发给n=150个黑白乳房 接受辅助治疗的癌症幸存者。这项调查，加上医疗记录数据，将 用于评估心理社会和社会文化因素与CTX的种族差异之间的关系。 为了成功地实现这些目标，候选人将接受癌症护理提供方面的战略规划， 心脏肿瘤学，以及混合方法研究。这些培训目标将确保候选人的目标是 成功过渡到独立，并建立了一个研究计划，涉及开发 将解决癌症护理提供和结果方面的种族差异的干预措施。专业知识和 除了丰富的资源和对培训的承诺外，指导和咨询团队的指导 通过机构环境提供的资金将确保候选人研究项目的成功和 向独立过渡。

Abstract The improvement in breast cancer survival is partially due to improvements in treatments. However, these treatments are not without mild to life-threatening side effects. For example, anthracycline chemotherapies (e.g. doxorubicin) and human epidermal growth factor receptor-2 (HER-2) targeted therapies have been shown to cause cardiotoxicity (CTX), or damage to the heart. This side effect is of great concern as survivors are more likely to die of heart disease than any other diagnosis and racial disparities exist with regard to prevalence of CTX and risk of heart-related mortality. Factors that have been shown to contribute to cardiotoxicity include Black race and the presence of comorbidities. While the cardiovascular disease literature includes the roles of psychosocial and sociocultural factors in its prevalence and the racial disparity in its manifestation and progression, these factors are unexplored in the context CTX. Additionally, cancer care delivery factors, including maintenance of CTX, deserves attention as there may be opportunities to address gaps or differences in care that may exacerbate the CTX disparity. Addressing psychosocial and sociocultural factors may provide intervention targets to mitigate CTX disparities. Guided by the Social Ecological Model, I will conduct retrospective analyses and a historical-prospective cohort study to identify factors related to the racial disparity in CTX. During the K99 mentored phase, I will abstract electronic hospital data on breast cancer survivors treated with anthracycline chemotherapy or Her-2 targeted therapies to elucidate sociodemographic, clinical, and maintenance factors that relate to onset of and racial differences in CTX (Aim 1). In Aim 2, I will conduct in-depth interviews with Black and White survivors (n=20) with and without CTX to understand psychosocial and sociocultural experiences that may contribute to CTX. During the R00 phase (Aim 3), I will use the information learned from the in-depth interviews to inform a survey that will be distributed to n=150 Black and White breast cancer survivors who were treated with adjuvant therapies. This survey, coupled with medical record data, will be used to assess relationships between psychosocial and socio-cultural factors and racial differences in CTX. In order to successfully execute these aims the candidate will receive strategic planning in cancer care delivery, cardio-oncology, and mixed methods research. These training aims will ensure the candidate's goal of successfully transitioning to independence and establishing a research program involving the development of interventions that will address racial disparities in cancer care delivery and outcomes. The expertise and guidance of the mentoring and advisory teams in addition to the wealth of resources and commitment to training provided through the institutional environment will ensure the success of the candidate's research project and transition to independence.